The proposed investigations include three related areas: (1) the interaction of hormone-receptor complexes with nucleotides; (2) role of nucleotides in the process of activation of receptors prior to their relocation at sites on nuclear chromatin; and (3) the interaction of hormone-receptor complexes with nuclear components of the target cells. Progesterone receptor has been shown to interact with ATP. This interaction will be studied in detail by using immobolized ATP on agarose columns. Comparable studies will also be conducted with estrogen receptor in target cells. The effects of certain inhibitors of DNA and RNA polymerase on uptake of progesterone receptor by isolated nuclei will be tested both in vivo and in vitro. The relationship between inhibitor action and ATP binding by the receptor will also be investigated. Attempts will be made to assess the role of nucleotides and inhibitors on the phenomenon of receptor activation and ATP binding. These studies are expected to provide significant correlation between such events as steroid binding by the receptor, receptor activation, and nuclear binding.